Effect of intensified chemotherapy on the pluripotent haematopoietic progenitor cells CFU‐GEMM in adult acute lymphoblastic leukaemia

Abstract

In order to analyse the short-term and long-term effects of intensified induction chemotherapy, the frequency, cellular composition and proliferative state of the pluripotent haemopoietic progenitor cells CFU-GEMM was investigated in a total of 35 patients with acute lymphoblastic or acute undifferentiated leukaemia at diagnosis, as well as during and after therapy. At diagnosis, the number of CFU-GEMM/ml bone marrow aspirate was significantly reduced to 12.1 (95% confidence interval 2.1-70) as compared to healthy controls (50.4/ml; 95% confidence interval 66-3846/ml). While immediately after the end of induction therapy, the respective values for CFU-GEMM were still decreased (30.4/ml; 95% confidence interval 8.4-108); values not significantly different from normal were reached within the following 4 weeks. During and after cessation of maintenance therapy again no significant deviation from normal values was observed. Immunological analysis of single colonies revealed that during the early phase after remission induction only 60 +/- 7% of mixed colonies contained megakaryocytic cells (normal 86 +/- 3%; P less than 0.01) while normal values were found during and after maintenance therapy. Cell cycle analysis disclosed highly increased proliferative activity of pluripotent progenitor cells during marrow regeneration after induction therapy as well as during maintenance therapy, but a return to the resting state after cessation of maintenance therapy. It is concluded that this intensive chemotherapy regimen does not result in any apparent long-term damage to the pluripotent haemopoietic progenitor cells.

Defective in vitro growth of the hemopoietic progenitor cells in the acquired immunodeficiency syndrome.

“…Contamination with peripheral blood and selective loss of progenitor cells during the cell separation procedures might further lead to unpredictable variability in the number of marrow progenitors, but to some extent the variability was controlled by limiting the volume of the bone marrow aspirate (29) and by the absence ofgross abnormalities in cellularity ofthe samples. Although the numbers of light-density MNC per milliliter aspirate were somewhat lower in the samples taken from the patients, this difference cannot account for the reduction in the in vitro colony formation, especially since there was no correlation between the number of colonies and the number of low-density cells per unit volume.…”

“…The assay for CFU-GEM and committed progenitor cells has been previously described (28,29 (31); erythroid bursts (BFU-E); and granulocyte-macrophage colonies (CFU-GM) were all scored from the same plates. Mixed colonies (CFU-GEM) could contain megakaryocytes, but this element was not especially quantitated in this study.…”

Long term hematopoeitic damage after chemotherapy and cytokine

“…In a similar experience, Osband et al reported that 7 of 17 patients treated by them with MeCCNU eventually went on to have severe, protracted hematologic compromise which included aplasia (11). Since then, there have been other reports of long-term chemotherapy-related marrow damage after the use of other chemotherapeutic agents, whether given alone or in combination with others: adriamycin with cyclophosphamide (12); a combined regimen of cyclophosphamide, methotrexate and 5-fluorouracil (12), mitoxantrone (13), and other regimens (14)(15)(16)(17).…”

Increased colony growth in peripheral blood cultures from patients with ALL depends on immunological subtype*

“…Colony formation in bone marrow cultures from ALL patients is known to be low (5-1 l), probably due to a "dilution" effect of precursor cells with lymphoblasts. On the other hand, colony formation in peripheral blood cultures from ALL patients has been found to be high in some patients (1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. It is not known why this phenomenon is not seen in all ALL patients (12,13).…”